This application addresses broad Challenge Area (04): Clinical Research and specific Challenge Topic 04-AG-107: Mechanisms of specific benefits of different types of physical activity. MECHANISMS AND FUNCTIONAL OUTCOMES OF EXERCISE PROGRESSION MODELS IN THE ELDERLY By 2030, the number of Americans 65 years or older will account for roughly 20% of the US population, with a projected increase in the Nation's health care spending of 25%. A major factor in the projected increase in health care costs is the consequences of a progressive decline in functional capacity with advancing age. The decline in functional capacity can be slowed with the help of exercise training as recommended by the American College of Sports Medicine (ACSM) and American Heart Association (AHA). Unfortunately, improvements in functional capacity, in the elderly are rather small, in part, because many elderly cannot tolerate sufficiently high intensity exercise due to orthopedic and cardiovascular limitations. Thus, despite some success, existing training strategies, for the elderly, appear less than optimal. Therefore, the challenge for our rapidly aging nation is to define interventions, for the elderly that can slow the decline in functional capacity and performance, prevent early onset of physical disability and loss of independence. The potential impact is a reduction in the probability of disease, disability, early mortality, and health care expenditures. We hypothesize that regionally specific exercise stimuli, applied at the beginning of a training program, will serve as a physiological primer capable of removing peripheral barriers that limit functional capacity, in elderly at risk of losing independence. Removal of peripheral barriers early in a training program will unlock a greater potential for change in functional capacity. Subsequently, the objectives of this proposal are twofold: (1) To determine differences between 4 weeks of a regionally specific exercise stimulus or standard aerobic exercise training on physical and functional performance;and (2) To determine the effects of subsequent 8 weeks of progressive whole- body training protocol on the magnitude of change in physical and functional performance. Of particular importance to these objectives is the combination of physiological information from biospecimens (vascular and muscular) with functional outcomes in the elderly, following two different types of exercise training progression models. Statement of Relevance By 2030, 20% of the US population will be >65 years old. Current training strategies for the elderly only show small effects on functional capacity. We will use a Regionally Specific Training Program to remove peripheral limitations and unlock a greater potential for change in functional capacity.